Today, more research than ever before is devoted for providing systems that can deliver a beneficial agent at a controlled rate of release to an environment of use over a specified period of time. For example, in U.S. Pat. Nos. 3,845,770 and 3,916,899 issued to inventors Felix Theeuwes and Takeru Higuchi, osmotic systems manufactured in the form of osmotic systems are disclosed for delivering a beneficial agent at a controlled rate to an environment of use. The systems disclosed in these patents comprise a semipermeable wall that surround a compartment containing the agent. The wall is permeable to an external fluid, substantially impermeable to agent, and there is a passageway through the wall for delivering the agent from the system. These systems release the agent by fluid being imbibed through the wall into the compartment, at a rate determined by the permeability of the wall and the osmotic pressure gradient across the wall, to produce a solution of the agent, that is dispensed through a passageway from the system. In U.S. Pat. No. 4,111,202, issued to Patentee Felix Theeuwes, an osmotic system is disclosed comprising a semipermeable wall that surrounds a first and second compartment. The first compartment contains a drug and the second compartment contains an osmotically effective solute. A passageway through the semipermeable wall connects the exterior of the system with the first compartment. The system releases agent by fluid being imbibed into the first compartment to prepare drug formulation and by fluid being imbibed into the second compartment causing it to increase in volume, expand into and decrease the volume of the first compartment, whereby the agent is delivered through the passageway from the system.
While the above systems are outstanding and represent a pioneer advancement in the delivery art, and while they are endowed with ideal delivery kinetics useful for delivering numerous and diverse beneficial agents at a controlled and continuous rate to many environments of use, there is an occasional instance where the delivery kinetics of the systems can be unexpectedly modified to lead to more desirable results. For example, one of the important factors that should be considered in designing a controlled release system is to maintain a constant thermodynamic activity of beneficial agent within the system. The pressure of this constant activity source establishes a steady state, so that agent is released from the system at a constant rate over time. This phenomenon is commonly referred to as zero order release.
If, however, a constant thermodynamic activity of agent is not maintained within the system and the released agent is not replenished, because the system lacks excess agent or a means for keeping the agent in a saturated state, the release rate falls exponentially and the amount of agent released can also become unpredictable over time. These latter conditions occur because less and less agent is available at the releasing diffusion boundary layer of the system and the quantity available for diffusion can be dependent on the degree of agitation. This release pattern is called first order release.
It wil be appreciated by those versed in the delivery art that in many applications, for example in the pharmaceutical, veterinary and agriculature industries, the zero order release is the most preferred release. This is so because precise delivery of an agent in known and constant amounts per unit time can lead to improve usage, and also in many instances minimize deleterious effects to the environment, organisms and plants. Also, through controlled release, the efficacy of agents may be enhanced, and the use of agents exhibiting high potencies or low stabilities may prove more managable and economical over time. It will be further appreciated in view of this presentation, that if a system is provided that can exhibit a substantially zero order release over time, the system would have a positive commercial use and also represent a major contribution to the delivery art.